Exploring elimination reactions

Elimination reactions involving amines are important synthetic methods. They can be used to make a variety of useful organic compounds, including alkenes. We examine a few of them in this section. 

The general mechanism forthe elimination in the Hofmann elimination. 

A sample reaction scheme forthe Hofmann elimination. 

Product distribution resulting from the Hofmann elimination. 

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If we want to perform a substitution reaction with an alcohol, we have the same issue that we had when we explored elimination reactions a few moments ago—the OH group is not a good leaving group. So, we must convert the OH into a better leaving group. There are several ways to do that for substitution reactions. We will look at four different ways ... 

In this chapter, we will explore elimination reactions in the same way that we explored substitution reactions. We begin with the mechanisms for El and E2 reactions, and then we move on to the factors that help us determine in each case which mechanism predominates. There is one big difference between the last chapter and this chapter. In the last chapter, most of the information was given to you, and there was very httle to look up in other sources (your textbook, your class notes, etc.). But now you know how important mechanisms are, you know that mechanisms explain everything, you know how to analyze different factors that affect reactions, and so on. So in this chapter, YOU are going to provide the key information, by filling it in the appropriate places. 

In the previous chapter, we saw that a substitution reaction can occur when a compound possesses a leaving group. In this chapter, we will explore another type of reaction, called elimination, which can also occur for compounds with leaving groups. In fact, substitution and elimination reactions frequently compete with each other, giving a mixture of products. At the end of this chapter, we will learn how to predict the products of these competing reactions. For now, let s consider the different outcomes for substitution and elimination reactions ... 

In a substitution reaction, the leaving group is replaced with a nucleophile. In an elimination reaction, a beta ((3) proton is removed together with the leaving group, forming a double bond. In the previous chapter, we saw two mechanisms for substitution reactions (SnI and Sn2). In a similar way, we will now explore two mechanisms for elimination reactions, called El and E2. Let s begin with the E2 mechanism. 

An El reaction is generally accompanied by a competing SnI reaction, and a mixture of products is generally obtained. At the end of this chapter, we will explore the main factors that affect the competition between substitution and elimination reactions. 

We mentioned that there are three main steps for predicting the products of substitution and elimination reactions. In the previous section, we explored the first step (determining the function of the reagent). In this section, we now explore the second step of the process in which we analyze the substrate and identify which mechanism(s) operates. 

The use of cyclic sulfates in synthetic applications has been limited in the past because, although cyclic sulfites are easily prepared from diols, a convenient method for oxidation of the cyclic sulfites to cyclic sulfates had not been developed. The experiments of Denmark [70] and of Lowe and co-workers [71 ] with stoichiometric ruthenium tetroxide oxidations and of Brandes and Katzenellenbogen [72a] and Gao and Sharpless [68] with catalytic ruthenium tetroxide and sodium periodate as cooxidant have led to an efficient method for this oxidation step. Examples of the conversion of several diols (67) to cyclic sulfites (68) followed by oxidation to cyclic sulfates (69) are listed in Table 6D.7. The cyclic sulfite/cyclic sulfate sequence has been applied to 1,2-, 1,3-, and 1,4-diols with equal success. Cyclic sulfates, like epoxides, are excellent electrophiles and, as a consequence of their stereoelectronic makeup, are less susceptible to the elimination reactions that usually accompany attack by nucleophiles at a secondary carbon. With the development of convenient methods for their syntheses, the reactions of cyclic sulfates have been explored, Most of the reactions have been nucleophilic displacements with opening of the cyclic sulfate ring. The variety of nucleophiles used in this way is already extensive and includes H [68], [68,73-76], F" [68,72,74], PhCOCT [68,73,74], NOJ [68], SCN [68],... 

Density functional theory and a high-level cib initio procedure (G2+) have been used to explore the potential energy surface for the base-induced elimination reaction of fluoride ion with ethyl fluoride.11 The DFT barriers are smaller and looser than those predicted by the ab initio method but the nature of the transition state cannot be defined with confidence since the predictions are unusually sensitive to the choice of functional and basis set. The results suggest that improvement in density functional methods will require fundamental change in the functionals themselves. 

The mechanistic borderline between E2 and ElcB mechanisms has been studied under various conditions.1,2 The mechanism of the elimination reaction of 2-(2-fluoroethyl)-1-methylpyridinium has been explored explored by Car-Parrinello molecular dynamics in aqueous solution.3 The results indicated that the reaction mechanism effectively evolves through the potential energy region of the carbanion the carbon-fluoride bond breaks only after the carbon-hydrogen bond. 

You will meet elimination reactions in the next chapter but one (19) after some further exploration of stereochemistry. 

The synergistic effect often observed in bimetallic systems was further explored by Garland and coworkers. The hydroformylation of 3,3-dimethylbut-l-ene to form 4,4-dimethylpentanal in >95% selectivity at room temperature with [Rli4(CO)i2]-[Mn2(CO)io/HMn(CO)5] as catalyst coprecursors was investigated using in situ PT-IR spectroscopic techniques and kinetic studies revealing evidence of a bimetallic catalytic binuclear elimination reaction (CBER). 

Unlike many families of molecules, the reactions of alcohols do not fit neatly into a single reaction class. In Chapter 9, we discuss only the substitution and P elimination reactions of alcohols. Alcohols are also key starting materials in oxidation reactions (Chapter 12), and their polar O - H bond makes them more acidic than many other organic compounds, a feature we will explore in Chapter 19. 

In the case of the attacks of neutral molecules on alkynes, nucleophilic attack is often difficult to distinguish from molecular cycloaddition or electrophilic initiation. Reaction (7) is typical of many which could equally as well be formulated as beginning with a dipolar cycloaddition or an acyclic zwitterion Detailed mechanism of these cycloaddition-elimination reactions remains to be explored... 3 . 

Further exploration of the regioselectivity of alkene formation in elimination reactions (ElcB anc E2). 

Sequential elimination reactions, most of them being dehydration, involving the reaction at the anomeric center often produce various aromatic compounds [235] especially furans which have diverse use [236,237]. Explorations have been continued to open a new route to aromatics based on renewable biomass in place of fossilized material. 

Chapter 5 considers the relationship between mechanism and regio- and stereoselectivity. The reactivity patterns of electrophiles such as protic acids, halogens, sulfur and selenium electrophiles, mercuric ion, and borane and its derivatives are explored and compared. These reactions differ in the extent to which they proceed through discrete carbocations or bridged intermediates and this distinction can explain variations in regio- and stereochemistry. This chapter also describes the El, E2, and Elcb mechanisms for elimination and the idea that these represent specific cases within a continuum of mechanisms. The concept of the variable mechanism can explain trends in reactivity and regiochemistry in elimination reactions. Chapter 6 focuses on the fundamental properties and reactivity of carbon nucleophiles, including... 

The early literature describes examples of elimination reactions of a rather forcing nature which have not been explored further. For example, the elimination of HCl from (2-chloroethyl)phosphonic dichloride occurs over BaCl2 at 330 and dechlorination of (l,2-dichloroethyl)phosphonic diesters occurs on heating with zinc dust. Dehydrochlorination of a (2-chloroalkyl)phosphonic acid occurs on simple pyrolysis but the preferred procedure consists in the treatment of the acid diester with Et3N in warm benzene, a procedure also used for analogous (2-chloroethyl)phosphinic esters ". The dehydro-halogenation of isopropyl (2-haloethyl)phenylphosphinate by a chiral tertiary amine, such as quinine, quinidine, 1 -phenylethylamine or A-methylephedrine, in a less than equivalent quantity, affords an enrichment of one enantiomer of the ethenylphenylphosphinic... 

In another work, Wentrup (this time in collaboration with the Tarczay s group, from Budapest), explored the photochemistiy of dimethylcarba-moyl azide in argon matrices. Broadband irradiation of the compound, using both xenon and mercuiy lamps, was found to lead to the sequential formation of dimethylamino isocyanate (MeaN-NCO), 1,1-dimethyldia-zene (Me2N=N), and ethane, via consecutive N2, CO and N2 elimination reactions (Fig. 35). Ethane formation was ascribed to recombination of methyl radicals. The obtained photoproducts were identified with the aid of quantum chemical calculations. This was the first experimental... 

Langer and colleagues explored the generation and cyclization of cyano-stabilized anions to give indoles and carbolines [44-46], For example, 5-carbolines were accessible via 2-alkyhdene-3-iminoindoles (Scheme 12, equations 1, 2) [45]. These workers uncovered the remarkable double domino cyclization/electrocyclization/elimination reaction (equation 3) [46], a fitting reaction to conclude this chapter ... 

As we begin now to explore the syntheses of carboxylic acid derivatives, we shall find that in many instances one acid derivative can be synthesized through a nucleophilic addition—elimination reaction of another. The order of reactivities that we have presented gives us a clue as to which syntheses are practical and which are not. In general, less reactive acyl compounds can be synthesissed from more reactive ones, but the reverse is usually difficult and, when possible, requires special reagents. 

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